This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plant secondary metabolites provide many leads for new therapeutics that are currently on the market. However, their mechanism of action is often not understood in either plants or animals. Our preliminary data show that, in Rubus, phenolics (a class of secondary metabolites) produced in the head structure of glandular trichomes are transported to cellular nuclei in the underlying stalk tissue. Due to the nuclear localization of these phenolics and the cell proliferative response that is subsequently induced, we hypothesize that the phenolics represent a new class of plant hormones that activate developmentally-regulated signal transduction pathways. We further hypothesize that these phenolics also are able to activate mammalian signaling pathways by mimicking small molecule ligands. In order to be competitive for further funding to test this hypothesis, we will be required to collect further preliminary data;therefore, we have formulated the following specific aims to: 1) Adapt and implement methods for cell cycle analyses for our plant tissues of interest and test the utility of these methods using plant secondary metabolites that are known to affect the cell cycle in plants; 2) Continue working on plant transformation technologies to enable the expression of genes that are involved in the cell cycle whose regulation may be altered by secondary metabolite exposure. These data will provide a pilot study to develop methods that will allow us to monitor cell cycle control in Rubus plant tissues, thus allowing further studies into the regulatory mechanisms for cell proliferation in plants and to compare these mechanisms with that in animals.